Illustration by Katherine Bilby
Research is the engine that drives modern medicine, and since 1999 the University of Louisville has made the largest gains of any university in research funds received from the National Institutes of Health. (The NIH is the primary government agency responsible for doling out medical research dollars). The university’s funding has nearly quadrupled and its rank has increased 30 places. Here are some of the most promising medical research projects currently under way at the University of Louisville School of Medicine and other local institutions, followed by a selected listing of clinical trials being conducted in the local medical community.
Increasing studies concerning toxic air pollutants have focused on cancer, asthma, birth defects and nervous system damage. However, new experimental and epidemiological data shows air toxins have pronounced effects on cardiovascular function and disease. Aruni Bhatnagar, a researcher at the U of L School of Medicine with a doctorate in chemistry, is leading a team of environmental cardiology investigators conducting studies that focus on compounds called aldehydes, which are generated from the burning of fossil fuels. Research has shown that high levels of aldehydes lead to inflammation of the heart and raise the risk of heart attack. The project’s aim is to understand how aldehydes metabolize and detoxify and how they exacerbate atherosclerosis (accumulation of arterial plaque). The study, which began two years ago, received a $7 million grant last year to ext/files/storyimages/the research.
Establishing new strategies in stem-cell research, Dr. Mariusz Ratajczak, director of the stem-cell biology program at the James Graham Brown Cancer Center, has identified cells in adult bone marrow that seem to behave like embryonic stem cells. This discovery, if the process proves to be practical, has the potential to change the face of this highly controversial field of research. The cells taken from adult bone marrow resemble embryonic stem cells and appear to mimic their ability to multiply and develop into other kinds of cells. Ratajczak’s team has been able to stimulate the cells to change into different types of nerve, heart and pancreas cells. The ongoing project holds much promise for reducing the need for embryonic cells in research and minimizing rejection problems connected with using stem cells from an outside donor.
The research of University of Louisville neuroscientist Fred Roisen could lead to new therapies for spinal-cord injury, multiple sclerosis, Parkinson’s disease, ALS and many other neurodegenerative disorders. Roisen’s team found that stem cells taken from the nasal passages of adult donors could transform into cells that s/files/storyimages/electrical signals from the brain to muscles. Working from the premise that the sense of smell is a primitive sense, Roisen, who holds a doctorate in developmental physiology, made the logical leap that nasal stem cells could serve as ancestors to other cells in the nervous system. Under laboratory conditions his team has been able to stimulate the nasal stem cells to become motoneurons — nerve cells that s/files/storyimages/electrical signals to muscles. The cells even began to form attachments with muscle tissue, hopeful evidence that it may be possible to regenerate connections between the nervous system and muscles that have been destroyed by disease.
The number of children with autism has doubled over the past 10 years — an alarming tr/files/storyimages/that brings urgency to studies conducted by University of Louisville neuroscientist Dr. Manuel Casanova. His team has found that tiny strands of connected brain tissue and the neurons between them vary in size, spacing and density in those with autism, dyslexia and other brain disorders. The researchers examined brain tissue samples from donors ranging in age from 10 weeks to 98 years old and created a model for predicting the growth rate of the strands before and after birth. This model could yield important clues pinpointing the origins and timing of brain abnormalities as they develop.
They say an ounce of prevention is worth a pound of cure, a sentiment at the core of a project by Brown Cancer Center researcher Ramesh C. Gupta that focuses on nutritional cancer prevention. Gupta’s research was the first to report on the effectiveness of berries against estrogen-related breast cancer and identify different berries that actually protect against breast and lung cancer. The beneficial-berry results found that blueberries cut the size of tumors by 50 percent in rats exposed to breast cancer. Black raspberries cut tumor growth by 60-70 percent, and a mix of strawberries, blackberries and black raspberries reduced the number of lung cancer cases and tumors in mice exposed to cigarette smoke by 30-35 percent. Gupta, whose Ph.D. is in biochemistry, is now working to develop a plan for human lung cancer trials in the next two years.
Clinical Trials
LEAP (Lower Extremity Atherosclerotic Plaque Excision)
Principal investigators: Dr. Matthew Jung, vascular surgeon, and Dr. Thomas Tu, interventional cardiologist.
Purpose: Evaluate plaque collected from patients with PAD (peripheral artery disease). The research will be used to identify biomarkers in plaque, which may provide insight to future treatment for patients affected by severe leg pain attributed to PAD.
Procedure: Patients enrolled in the study will have SilverHawk (a device, which uses a tiny rotating blade to shave away large amounts of plaque from inside leg arteries) excision in one leg, receive one of the study drugs or a placebo for a period of time, then have the plaque removed in the other leg.
Participating Hospitals: Baptist Hospital East and Central Baptist Hospital in Lexington.
SELECT (Selenium and Vitamin E Cancer Prevention Trial)
Principal investigators: Urologists Dr. Kerry Short and Dr. Christopher Smith.
Purpose: The study will determine if selenium and vitamin E help prevent prostate cancer. Laboratory research has shown selenium and vitamin E to have a protective effect against cancer.
Procedure: During the double-blind, placebo-controlled study, men will be randomly selected to receive either: some combination of selenium, vitamin E or placebo. The trial is expected to take five years, with seven years of follow up.
Participating hospital: Baptist Hospital East.
ALIAS (Albumin in Acute Stroke)
Principal investigator: Neurologists Dr. James M. Gebel Jr. and sub-investigator Dr. Ulises Nobo.
Purpose: Evaluate the effectiveness of high-dose human serum albumin (a natural protein in clinical use for a variety of indications) administered intravenously. In animal laboratory studies it has reduced the size of the infarction (amount of tissue death) in the brain and improved neurological function after stroke. It also decreased or eliminated swelling of the brain — these effects may reduce or prevent the brain damage resulting from a stroke in humans.
Procedure: Subjects must give consent and meet certain criteria at the onset of symptoms. Approved patients will receive the study medication or placebo. A schedule of brain x-rays and ECG tests are performed with follow-up lasting seven days
Participating hospital: Jewish Hospital.
DIAS2 (Desmoteplase in Acute Ischemic Stroke)
Principal Investigator: Neurologist Dr. James Gebel Jr., and sub-investigators Dr. Ulises Nobo and Dr. Richard Paulsen.
Purpose: The study will investigate the potential of desmoteplase (a genetically engineered version of a clot-busting agent found in vampire bat saliva) to treat acute ischemic stroke patients up to nine hours after the onset of a stroke — three times longer than the current available treatment allows.
Procedure: At the onset of symptoms, patients meeting test criteria and giving consent will receive the study medication or placebo. Scheduled CT scans will monitor the final results of the brain tissue damaged. Subjects will have a follow-up of two months.
Participating hospital: Jewish Hospital
Effect of Roflumilast on Exacerbation Rate in Patients with COPD
Principal investigator: Dr. Eugene Fletcher, pulmonologist.
Purpose: Roflumilast is a drug that has very strong anti-inflammatory functions. The study will investigate if patients taking the drug have fewer episodes of exacerbation of their COPD (Chronic Obstructive Pulmonary Disease).
Procedure: A 52-week, double-blind study where participants take a placebo or Roflumilast.
Participating hospital: Floyd Memorial Hospital.
Soft-Tissue Sarcoma Trial
Principal investigator: Dr. John Hamm, oncologist.
Purpose: To facilitate access to a new drug for subjects not benefiting from other medications.
Procedure: This is an expanded access protocol for patients who have exhausted other cancer treatments. The study consists of two phases and the medication is admistered intravenously.
Participating facility: Louisville Oncology, part of Norton Cancer Center. .
